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Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease that results in immune cell infiltration of the central nervous system (CNS) and demyelination in young adults. Substantial progress has been made in developing disease modifying therapies for people with relapsing-remitting MS, but options remain limited for people with primary progressive MS (PPMS). PPMS accounts for ∼15% of MS diagnoses. Herein, we generated a human induced pluripotent stem cell line (hiPSC) from a person with clinically definite PPMS. This disease-specific hiPSC line will be useful for studying PPMS in vitro, allowing the generation of immune and CNS cell types.

ABSTRACT: Dietary carbohydrate manipulation can be used to reduce enteric CH4 emission, but few studies have focused on the interaction of the different types of carbohydrates that can affect feed intake and ruminal fermentation. Understanding this interaction is necessary to make the most out of CH4 mitigation feeding strategies using different dietary carbohydrates. The aim of this study was to test the effect on enteric CH4 emission, feed intake, and milk production response when cows were fed either grass-clover silage (GCS) or corn silage (CS) as the sole forage source (55% of dry matter, DM), in combination with either barley (BAR) or dried beet pulp (DBP) as a concentrate (21.5% of DM). A total of 24 (half first-parity and half second-parity) cows were used in a crossover design with 2 periods of 21 d each, receiving 2 of 4 diets obtained from a 2 × 2 factorial arrangement of the experimental diet. Feed intake, CH4 emission metrics, and milk production were recorded at the end of the experimental periods. The diets had NDF concentrations between 258 and 340 g/kg of DM and starch concentrations between 340 and 7.45 g/kg of DM (CS-BAR and GCS-DBP, respectively). The effects of silage and concentrate on dry matter intake (DMI) were additive, with the highest feed intake in cows fed CS-BAR, followed by cows fed CS-DBP, GCS-BAR, and GCS-DBP (21.2, 19.9, 19.1, and 18.3 kg/d, respectively). Energy corrected milk (ECM) yield was not affected by silage source in first parity cows, but it was higher for cows fed CS than cows fed GCS in second parity. The effects of silage and concentrate on CH4 production (g/d), yield (g/kg of DMI), and intensity (g/kg of ECM) were not additive, as cows fed GCS had similar responses regardless of the concentrate used, but cows fed CS had lower CH4 production, yield, and intensity when fed BAR instead of DBP. The lower CH4 production, yield, and intensity in cows fed CS-BAR compared with other diets could be partially explained by the nonlinear relationship between ruminal VFA and carbohydrates (NDF and starch) concentration reported in the literature; however, we observed a linear relationship between the acetate/propionate ratio and CH4 yield, suggesting possible other effects. The effects of silage and concentrate on the ruminal VFA were additive in first parity cows, but not in second parity cows. The interaction between dietary carbohydrate type and parity might indicate an effect of feed intake or the energy balance of the cow. Feeding cows silage and concentrate both rich in starch can result in the lowest enteric CH4 emission.

Background: Electrogram dispersion identifies putative atrial fibrillation (AF) drivers in first time ablation procedures, with high acute termination rates and long-term outcomes akin to extensive ablation approaches. Its use in a population that had undergone repeat ablation is unknown, particularly where the pulmonary veins are already isolated. Objective: This purpose of this study was to assess electrogram dispersion mapping during repeat ablation procedures for persistent AF. Methods: One hundred sixty-seven patients from the United Kingdom and Denmark, all with persistent AF recurrence after prior ablation procedure(s), were mapped using a five splined catheter for electrogram dispersion before ablation. Areas were manually tagged on biatrial electroanatomic maps and ablated once pulmonary vein isolation was confirmed or reisolated if required. All patients had 12-month continuous monitoring, with most of the cohort having follow-up beyond 24 months. Results: Of the 167 patients [53 (32%) female; mean age 66 ± 8 years; mean left atrial (LA) diameter 4.8 cm; mean ejection fraction 53%], 108 had pulmonary veins already isolated. Dispersion sites occurred in both atria (3.2 LA, 1.4 right atrium). Acute termination to sinus rhythm occurred in 71 (42%) of the cohort patients, with a further 73 (44%) terminating to atrial tachycardia/flutter. At 12-month follow-up, 95% of patients were free of AF, with 74% overall freedom from all atrial arrhythmias. Heart failure and severely enlarged LA predicted recurrence, and termination to sinus improved freedom from all atrial arrhythmias. Conclusion: Dispersion mapping is a promising approach at repeat ablation procedures for persistent AF, with high acute termination rates and good clinical outcomes. Further prospective randomized trials are needed to evaluate this approach in a population that had undergone repeat ablation.

ABSTRACT: Enteric CH4 produced from dairy cows contributes to the emission of greenhouse gases from anthropogenic sources. Recent studies have shown that the selection of lower CH4-emitting cows is possible, but doing so would be simpler if performance measures already recorded on farm could be used, instead of measuring gas emissions from individual cows. These performance measures could be used for selection of low emitting cows. The aim of this analysis was to quantify how much of the between-cow variation in CH4 production can be explained by variation in performance measures. A dataset with 3 experiments and a total of 149 lactating dairy cows with repeated measures was used to estimate the between-cow variation (the variation between cow estimates) for performance and gas measures from GreenFeed (C-Lock, Rapid City, SD). The cow estimates were obtained with a linear mixed model with the diet within period effect as a fixed effect and the cow within experiment as a random effect. The cow estimates for CH4 production were first regressed on the performance and gas measures individually, and then performance and CO2 production measures were grouped in 3 subsets for principal component analysis and principal component regression. The variables that explained most of the between-cow variation in CH4 production were DMI (R2 = 0.44), among the performance measures, and CO2 production (R2 = 0.61), among gas measures. Grouping the measures increased the R2 to 0.53 when only performance measures were used, and to 0.66 when CO2 production was added to the significant performance measures. We found the marginal improvement to be insufficient to justify the use of grouped measures rather than an individual measure because the latter simplifies the model and avoids over-fitting. Investigation of other measures that can be explored to increase explanatory power of between-cow variation in CH4 production is briefly discussed. Finally, the use of residual CH4 as a measure for CH4 efficiency could be considered by using either DMI or CO2 production as the sole predicting variables.

ABSTRACT: Fat in the form of cracked rapeseed and 3-nitrooxypropanol (3-NOP, market as Bovaer) were fed alone or in combination to 4 Danish Holstein multicannulated dairy cows, with the objective to investigate effects on gas exchange, dry matter intake (DMI), nutrient digestion, and nutrient metabolism. The study design was a 4 × 4 Latin square with a 2 × 2 factorial treatment arrangement with 2 levels of fat supplementation; 33 g of crude fat per kg of dry matter (DM) or 64 g of crude fat per kg of DM for low and high fat diets, respectively, and 2 levels of 3-NOP; 0 mg/kg DM or 80 mg/kg DM. In total, 4 diets were formulated: low fat (LF), high fat (HF), 3-NOP and low fat (3LF), and 3-NOP and high fat (3HF). Cows were fed ad libitum and milked twice daily. The adaptation period lasted 11 d, followed by 5 d with 12 diurnal sampling times of digesta and ruminal fluid. Thereafter, gas exchange was measured for 5 d in respiration chambers. Chromic oxide and titanium dioxide were used as external flow markers to determine intestinal nutrient flow. No interactions between fat supplementation and 3-NOP were observed for methane yield (g/kg DM), total-tract digestibility of nutrients or total volatile fatty acid (VFA) concentration in the rumen. Methane yield (g/kg DMI) was decreased by 24% when cows were fed 3-NOP. In addition, 3-NOP increased carbon dioxide and hydrogen yield (g/kg DM) by 6% and 3,500%, respectively. However, carbon dioxide production was decreased when expressed on a daily basis. Fat supplementation did not affect methane yield but tended to reduce methane in percent of gross energy intake. A decrease (11%) in DMI was observed, when cows were fed 3-NOP. Likely, the lower DMI mediated a lower passage rate causing the tendency to higher rumen and total-tract neutral detergent fiber digestibility, when the cows were fed 3-NOP. Total VFA concentrations in the rumen were negatively affected both by 3-NOP and fat supplementation. Furthermore, 3-NOP caused a shift in the VFA fermentation profile, with decreased acetate proportion and increased butyrate proportion, whereas propionate proportion was unaffected. Increased concentrations of the alcohols methanol, ethanol, propanol, butanol, and 2-butanol were observed in the ruminal fluid when cows were fed 3-NOP. These changes in rumen metabolites indicate partial re-direction of hydrogen into other hydrogen sinks, when methanogenesis is inhibited by 3-NOP. In conclusion, fat supplementation did not reduce methane yield, whereas 3-NOP reduced methane yield, irrespective of fat level. However, the concentration of 3-NOP and diet composition and resulting desired mitigation effect must be considered before implementation. The observed reduction in DMI with 80 mg 3-NOP/kg DM was intriguing and may indicate that a lower dose should be applied in a Northern European context; however, the mechanism behind needs further investigation.

Well-aligned food policies are needed at both national and international level to guide food system transformation towards sustainability. Rigorous indicator frameworks are essential in order to facilitate discussion of priorities, enable comparisons, assessment and progress monitoring, and ensure accountability. In this study, we develop a national framework for a sustainable food system, using Sweden as a case. Our framework, the Food System Sustainability House, advances the literature on sustainable food system frameworks in three distinct ways. Firstly, it is tailored to a specific national context (Sweden in our case); secondly, it distinguishes between impacts of domestic production arising within territorial boundaries and impacts related to Swedish consumption independent of country of origin; and thirdly, to facilitate policy priorities, it suggests how different dimensions of sustainability are interlinked at a conceptual level. From a scientific perspective, the Food System Sustainability House postulates the interlinkages between the societal objectives of the food system, the environmental foundations on which production takes place, and the economic system and governance which in the framework are suggested to function as enablers for an overall sustainable system. From a policy perspective, the framework provides a much-needed basis for assessing food system sustainability by suggesting indicators within a comprehensive set of sustainability themes at national level for monitoring distinct perspectives. It also provides the necessary basis for a discussion on how sustainability dimensions are interlinked.

Background: No previous study has evaluated patients attitudes towards inclusion in an ongoing cardiac arrest clinical trial. The aim of this study was to assess patientś willingness and motives to participate in the ongoing randomized controlled drug trial “Vasopressin and Steroids in addition to Adrenaline in cardiac arrest” (VAST-A trial) in case of an in-hospital cardiac arrest (IHCA). Objectives: Hospitalized patients, men ≥ 18 and women ≥ 50 years, were asked for informed consent for inclusion in the VAST-A trial in case of an IHCA, the reason for approving or declining inclusion in the trial and baseline characteristics. Methods: Patients admitted to hospital were asked to give informed consent of inclusion in VAST-A in case of an IHCA during their hospital stay. Patients were also asked why they approved or declined inclusion as well as baseline characteristics questions. Results: 1,064 patients were asked about willingness to participate in the VAST-A trial, of these 902 (84.8%) patients approved inclusion. A subgroup of 411 patients were, except willingness, also asked about motives to participate or not and basic characteristics. The main reason for approving inclusion was to contribute to research (n = 328, 83.9%). The main reason for declining inclusion was concerns regarding testing the drug treatment (n = 6, 30%). Conclusion: Among hospitalized patients the vast majority gave informed consent to inclusion in an ongoing randomized cardiac arrest drug trial. The main reason for approving inclusion was to contribute to research.

ABSTRACT: The objective of the present study was to investigate the effect of individual and combined use of dietary fat, nitrate, and 3-nitrooxypropanol (3-NOP) on dairy cows' enteric methane (CH4) emission and production performance. Twenty-four primiparous and 24 multiparous Danish Holstein cows (111 ± 44.6 d in milk; mean ± standard deviation) were included in an incomplete 8 × 8 Latin square design with six 21-d periods. Dietary treatments were organized in a 2 × 2 × 2 factorial arrangement aiming for 2 levels of FAT (30 or 63 g of crude fat/kg of dry matter [DM]; LF or HF, respectively), 2 levels of NITRATE (0 or 10 g of nitrate/kg of DM; UREA or NIT, respectively), and 2 levels of 3-NOP (0 or 80 mg/kg DM; BLANK or NOP, respectively). Treatments were included in ad libitum-fed partial mixed rations in bins that automatically measured feed intake and eating behavior. Additional concentrate was offered as bait in GreenFeed units used for measurement of gas emission. For total DM intake (DMI), a FAT × NITRATE interaction showed that DMI, across parities and levels of 3-NOP, was unaffected by separate fat supplementation, but reduced by nitrate with 4.6% and synergistically decreased (significant 2-way interaction) with 13.0% when fat and nitrate were combined. Additionally, 3-NOP decreased DMI by 13.4% and the combination of 3-NOP with fat and nitrate decreased DMI in an additive way (no significant 3-way interaction). The decreasing effects on DMI were more pronounced in multiparous cows than in primiparous cows. For treatments with largest reductions in DMI, eating behavior was altered toward more frequent, but smaller meals, a slower eating rate and increased attempts to visit unassigned feed bins. Energy-corrected milk (ECM) yield increased by 6.3% with fat supplementation, whereas ECM yield did not differ among diets including nitrate (FAT × NITRATE interaction). Cows supplemented with 3-NOP had 9.0% lower ECM yield than cows fed no 3-NOP. Based on three 2-way interactions including FAT, NITRATE, and 3-NOP, the combined use of the additives resulted in antagonistic effects on CH4 reduction. A 6% to 7% reduction in CH4 yield (CH4/kg of DMI) could be ascribed to the effect of fat, a 12% to 13% reduction could be ascribed to the effect of nitrate and an 18% to 23% reduction could be ascribed to the effect of 3-NOP. Hence, no combinations of additives resulted in CH4 yield-reductions that were greater than what was obtained by separate supplementation of the most potent additive within the combination. The CH4 yield reduction potential of additives was similar between parities. Increased apparent total-tract digestibility of organic matter (OM) in cows fed combinations including nitrate or 3-NOP was a result of a NITRATE × 3-NOP interaction. Apparent total-tract digestibility of OM was also increased by fat supplementation. These increases reflected observed decreases in DMI. In conclusion, combined use of fat, nitrate, and 3-NOP in all combinations did not result in CH4 reductions that were greater than separate supplementation of the most potent additive within the combination (3-NOP > nitrate > fat). Additionally, separate supplementation of some additives and combined use of all additives reduced DMI.

Background: In neurologic prognostication of comatose survivors from cardiac arrest, two independent predictors of poor outcome are the loss of the Pupillary light reflex (PLR) and the loss of the N20 response from Somatosensory Evoked potentials (SSEP). The PLR can be quantitatively assessed by pupillometry. Both tests depend on the midbrain, in which a dysfunction reflects a severe hypoxic injury. We reasoned that a certain level of defective PLR would be predictive of a bilaterally absent SSEP N20 response. Method: Neurological Pupil index (NPi) from the pupillometry and the SSEP N20 response were registered >48 h after cardiac arrest in comatose survivors. Clinical data were retrospectively analyzed. A receiver operating characteristic curve was used to evaluate the capacity of NPi to predict bilaterally absent SSEP N20 response. An NPi threshold value resulting in 48 hours after cardiac arrest predicted bilateral loss of the SSEP N20 response with a FPR

ABSTRACT: The objective was to investigate the effect of nonprotein nitrogen source, dietary protein supply, and genetic yield index on methane emission, N metabolism, and ruminal fermentation in dairy cows. Forty-eight Danish Holstein dairy cows (24 primiparous cows and 24 multiparous cows) were used in a 6 × 4 incomplete Latin square design with 4 periods of 21-d duration. Cows were fed ad libitum with the following 6 experimental diets: diets with low, medium, or high rumen degradable protein (RDP):rumen undegradable protein (RUP) ratio (manipulated by changing the proportion of corn meal, corn gluten meal, and corn gluten feed) combined with either urea or nitrate (10 g NO3−/kg of dry matter) as nonprotein nitrogen source. Samples of ruminal fluid and feces were collected from multiparous cows, and total-tract nutrient digestibility was estimated using TiO2 as flow marker. Milk samples were collected from all 48 cows. Gas emission (CH4, CO2, and H2) was measured by 4 GreenFeed units. We observed no significant interaction between dietary RDP:RUP ratio and nitrate supplementation, and between nitrate supplementation and genetic yield index on CH4 emission (production, yield, intensity). As dietary RDP:RUP ratio increased, intake of crude protein, RDP, and neutral detergent fiber and total-tract digestibility of crude protein linearly increased, and RUP intake linearly decreased. Yield of milk, energy-corrected milk, and milk protein and lactose linearly decreased, whereas milk fat and milk urea nitrogen concentrations linearly increased as dietary RDP:RUP ratio increased. The increase in dietary RDP:RUP ratio resulted in a linear increase in the excretion of total purine derivatives and N in urine, but a linear decrease in N efficiency (milk N in % of N intake). Nitrate supplementation reduced dry matter intake (DMI) and increased total-tract organic matter digestibility compared with urea supplementation. Nitrate supplementation resulted in a greater reduction in DMI and daily CH4 production and a greater increase in daily H2 production in multiparous cows compared with primiparous cows. Nitrate supplementation also showed a greater reduction in milk protein and lactose yield in multiparous cows than in primiparous cows. Milk protein and lactose concentrations were lower for cows receiving nitrate diets compared with cows receiving urea diets. Nitrate supplementation reduced urinary purine derivatives excretion from the rumen, whereas N efficiency tended to increase. Nitrate supplementation reduced proportion of acetate and propionate in ruminal volatile fatty acids. In conclusion, no interaction was observed between dietary RDP:RUP ratio and nitrate supplementation, and no interaction between nitrate supplementation and genetic yield index on CH4 emission (production, yield, intensity) was noted. Nitrate supplementation resulted in a greater reduction in DMI and CH4 production, and a greater increase in H2 production in multiparous cows than in primiparous cows. As the dietary RDP:RUP ratio increased, CH4 emission was unaffected and RDP intake increased, but RUP intake and milk yield decreased. Genetic yield index did not affect CH4 production, yield, or intensity.

In-process inspection of the additive manufacturing process requires a technique that can provide reliable measurements given the extreme operating environments, the small size of the defects and the cyclic melting and heating of the material, caused by subsequently deposited layers. A remote and couplant-free ultrasonic inspection technique using bulk waves that can image near-surface defects could address these in-process inspection requirements. Laser induced phased arrays (LIPA) generate and detect ultrasound based on laser ultrasonics principles, while the array is synthesised in post-processing. However, when using LIPAs for inspection, the surface acoustic waves (SAWs) interfere with the bulk wave modes giving rise to crosstalk and artefacts, which makes near-surface defect imaging difficult. This work experimentally validates and compares five techniques for SAW suppression: amplitude thresholding, mean waveform subtraction, principal component subtraction, frequency-wavenumber filtering, and phase coherence imaging. SAW suppression is demonstrated in ultrasonic images of transverse waves based on 71-element LIPA data synthesised on a Ti-6Al-4V directed energy deposition-arc (DED-Arc/Ti6Al4V) sample with a ∼1 mm diameter side drilled hole, located at ∼4 mm below the inspected surface. The reported results show that the principal component subtraction approach achieved the highest ‘signal-to-crosstalk ratio’ improvement of 16 dB, while successfully suppressing the SAW.

Summary: Motor neuron (MN) development and nerve regeneration requires orchestrated action of a vast number of molecules. Here, we identify SorCS2 as a progranulin (PGRN) receptor that is required for MN diversification and axon outgrowth in zebrafish and mice. In zebrafish, SorCS2 knockdown also affects neuromuscular junction morphology and fish motility. In mice, SorCS2 and PGRN are co-expressed by newborn MNs from embryonic day 9.5 until adulthood. Using cell-fate tracing and nerve segmentation, we find that SorCS2 deficiency perturbs cell-fate decisions of brachial MNs accompanied by innervation deficits of posterior nerves. Additionally, adult SorCS2 knockout mice display slower motor nerve regeneration. Interestingly, primitive macrophages express high levels of PGRN, and their interaction with SorCS2-positive motor axon is required during axon pathfinding. We further show that SorCS2 binds PGRN to control its secretion, signaling, and conversion into granulins. We propose that PGRN-SorCS2 signaling controls MN development and regeneration in vertebrates.

Background: Multiple domains of quality of life (QoL) such as erectile function are not sufficiently investigated among left ventricular assist-device (LVAD) patients. We aimed to evaluate the prevalence of erectile dysfunction (ED) and its association with QoL and depression. Methods: This is a prospective, single-center, cross-sectional study. We included adult male LVAD patients who were clinically stable after at least 3 months post-implantation. Erectile function was assessed with the International Index of Erectile Function (IIEF-5) questionnaire with a score of ≤21 being confirmatory for ED. QoL and depression were estimated with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Patient Health Questionnaire depression scale (PHQ-8), respectively. Results: The study included 56 patients, of whom 45 (80 %) met criteria for ED, a prevalence much higher than previously reported in patients with established cardiovascular disease or conservatively treated heart failure. Patients with ED were older and had lower 6-minute walking distance. ED was not associated with comorbidities and heart failure medications but with less frequent use of diuretics and phosphodiesterase-5 inhibitors. There was a correlation between erectile function and depression as well as QoL. Conclusions: These findings underscore that ED deserves special attention and should be included in a multi-targeted approach to address suboptimal QoL outcomes after LVAD implantation.

Introduction: Organ shortage, subsequent use of extended donor criteria organs and high-risk recipients needing redo-surgery are increasing the complexity of heart transplantation. Donor organ machine perfusion (MP) is an emerging technology allowing reduction of ischemia time as well as standardized evaluation of the organ. The aim of this study was to review the introduction of MP and analyze the results of heart transplantation after MP in our center. Methods: In a retrospective single-center study, data from a prospectively collected database were analysed. From July 2018 to August 2021, fourteen hearts were retrieved and perfused using the Organ Care System (OCS), 12 hearts were transplanted. Criteria to use the OCS were based on donor/recipient characteristics. Primary objective was 30-day survival, secondary objectives were major cardiac adverse events, graft function, rejection episodes as well as overall survival in the follow-up and assessment of MP technical reliability. Results: All patients survived the procedure and the postoperative 30-day interval. No MP related complications were noted. Graft ejection fraction beyond 14 days was ≥ 50% in all cases. Endomyocardial biopsy showed excellent results with no or mild rejection. Two donor hearts were rejected after OCS perfusion and evaluation. Conclusion: Ex vivo normothermic MP during organ procurement is a safe and promising technique to expand the donor pool. Reduction of cold ischemic time while providing additional donor heart assessment and reconditioning options increased the number of acceptable donor hearts. Additional clinical trials are necessary to develop guidelines regarding the application of MP.

Background: Extra Corporeal Life Support (ECLS) is an evolving therapy in therapy-resistant cardiogenic shock (CS). Vascular cannulation in emergency situations can be accomplished through puncture of the femoral vessels by specialised teams. Since lower limb ischemia constitutes one of the major complications following cannulation, a distal perfusion cannula (DPC) has emerged as standard of care. We here aimed to analyse the impact of the DPC on limb perfusion and 6-month survival rate. Methods: In a retrospective study from January 2012 to December 2018, 98 patients with cardiogenic shock and peripheral (v-a) ECLS implantation with documented limb perfusion status were identified and analysed. Demographic data, laboratory parameters, cause of CS, comorbidities, limb perfusion complications and complication management were analysed. Results: 53 patients (54%) received ECLS therapy in referral centers by our mobile ECLS team, while in 45 patients (46%) the cannulation occured in our center. 71 patients (72%) received a DPC (group A) at the time of ECLS implantation, whereas 27 (28%) (group B) did not or received later (14 patients owing to limb ischemia). 44 patients (45%) developed limb ischemia as a complication of ECLS therapy (31% in group A and 81% in group B- p

Background and purpose: A brain tumour, especially a glioma, is a rare disease; it is challenging to treat and the prognosis is often poor. Routine care includes surgery and concomitant chemoradiotherapy (CRT). Diagnostic work-up and treatment effects are typically evaluated using magnetic resonance imaging (MRI). Quantitative MRI (qMRI), unlike conventional MRI, has the advantage of providing tissue-specific relaxation rates and proton density. The purpose is to detect changes in normal appearing white matter (NAWM) in brain tumour patients after CRT using qMRI. Materials & methods: NAWM was analysed in 10 patients, in 83 MR examinations performed before and after surgery and after CRT. Relaxation rates R1 and R2, the proton density (PD) and the concentration of myelin (cMy) were calculated from the qMRI scans and analysed in correlation to radiation dose and time after treatment. Results: A significant decrease in cMy between pre-treatment imaging and first follow-up and an increase in PD were observed. For low doses (less than 30 Gy) PD and cMy returned to baseline (=pre-operative status), while for high doses (>30 Gy) the change increased during the full extent of the follow-up period. No difference could be established for R1. For R2 an increase was observed during the first year, which then gradually returned to baseline. For R2, stronger effects were seen as a consequence of higher absorbed doses. Conclusion: In the long-term follow-up for glioma patients, qMRI is a powerful tool for detecting small changes, such as a decrease of myelin concentration, in NAWM after CRT.

Summary: Coat protein complex II (COPII) plays an integral role in the packaging of secretory cargoes within membrane-enclosed transport carriers that leave the endoplasmic reticulum (ER) from discrete subdomains. Lipid bilayer remodeling necessary for this process is driven initially by membrane penetration mediated by the Sar1 GTPase and further stabilized by assembly of a multilayered complex of several COPII proteins. However, the relative contributions of these distinct factors to transport carrier formation and protein trafficking remain unclear. Here, we demonstrate that anterograde cargo transport from the ER continues in the absence of Sar1, although the efficiency of this process is dramatically reduced. Specifically, secretory cargoes are retained nearly five times longer at ER subdomains when Sar1 is depleted, but they ultimately remain capable of being translocated to the perinuclear region of cells. Taken together, our findings highlight alternative mechanisms by which COPII promotes transport carrier biogenesis.

Purpose: Radiation therapy (RT) is an integral part of treatment concepts for early-stage Hodgkin lymphoma. This analysis reports on RT quality in the recent HD16 and 17 trials of the German Hodgkin Study Group (GHSG). Methods and Materials: All RT plans of involved-node radiation therapy (INRT) in HD 17 were requested for analysis, along with 100 and 50 involved-field radiation therapy (IFRT) plans in HD 16 and 17, respectively. A structured assessment regarding field design and protocol adherence was performed by the reference radiation oncology panel of the GHSG. Results: Overall, 100 (HD 16) and 176 (HD 17) patients were eligible for analysis. In HD 16, 84% of RT series were evaluated as correct, with significant improvement compared with the predecessor studies (P < .001). In HD 17, 76.1% of INRT cases revealed a correct RT design compared with 69.0% of IFRT-cases, which was superior to previous studies (P < .001). Comparing INRT and IFRT, we found no significant differences in the percentage of any deviation (P = .418) or major deviations (P = .466). Regarding dosimetry, INRT was accompanied by an improvement in thyroid doses. Comparing different RT techniques, we found that intensity-modulated RT showed a reduction of high doses in the lung at the expense of an increased low-dose exposure in HD 17. Conclusions: The latest study generation of the GHSG demonstrates an improved quality in RT. A modern INRT design could be established without deterioration in quality. On a conceptual level, an individual consideration of the appropriate RT technique has to be performed.

Summary: Background: A prediction model that estimates survival and neurological outcome in out-of-hospital cardiac arrest patients has the potential to improve clinical management in emergency rooms. Methods: We used the Swedish Registry for Cardiopulmonary Resuscitation to study all out-of-hospital cardiac arrest (OHCA) cases in Sweden from 2010 to 2020. We had 393 candidate predictors describing the circumstances at cardiac arrest, critical time intervals, patient demographics, initial presentation, spatiotemporal data, socioeconomic status, medications, and comorbidities before arrest. To develop, evaluate and test an array of prediction models, we created stratified (on the outcome measure) random samples of our study population. We created a training set (60% of data), evaluation set (20% of data), and test set (20% of data).We assessed the 30-day survival and cerebral performance category (CPC) score at discharge using several machine learning frameworks with hyperparameter tuning. Parsimonious models with the top 1 to 20 strongest predictors were tested. We calibrated the decision threshold to assess the cut-off yielding 95% sensitivity for survival. The final model was deployed as a web application. Findings: We included 55,615 cases of OHCA. Initial presentation, prehospital interventions, and critical time intervals variables were the most important. At a sensitivity of 95%, specificity was 89%, positive predictive value 52%, and negative predictive value 99% in test data to predict 30-day survival. The area under the receiver characteristic curve was 0.97 in test data using all 393 predictors or only the ten most important predictors. The final model showed excellent calibration. The web application allowed for near-instantaneous survival calculations. Interpretation: Thirty-day survival and neurological outcome in OHCA can rapidly and reliably be estimated during ongoing cardiopulmonary resuscitation in the emergency room using a machine learning model incorporating widely available variables. Funding: Swedish Research Council (2019–02019); Swedish state under the agreement between the Swedish government, and the county councils (ALFGBG-971482); The Wallenberg Centre for Molecular and Translational Medicine.

The age and character of the main unconformities offshore Palawan is resolved, and their history reviewed. Some very deep and very shallow unconformities have insufficient well data, but from the Oligocene to Late Miocene times a series of unconformities can be dated, characterised and correlated regionally to help develop a new tectono-stratigraphic framework. This framework does not support the widely cited idea of Early Miocene subduction of a Proto-South China Sea plate followed by collision over a plate suture.The absence or very weak expression of a Base Miocene Unconformity (c. 24 Ma), so strongly expressed across northern Borneo, also suggests a major revision of tectonic models is required. In spite of many cited reports, there is no evidence for an unconformity in the later Early Miocene (c. 17 to 15 Ma), which was a period of gradually increasing compression and uplift. The main mid-Neogene seismic unconformity is the Red Unconformity dated at about 12–13 Ma (equivalent to the DRU of Sabah). This was when the uplift of a foreland over-thrust system paused, and a locally erosional surface was rapidly transgressed.This review describes the neglect of analytical sciences that remain a crucial part of basic geological studies.

Background: Identifying signs of medical distress prior to in-hospital cardiac arrest (IHCA) is important to prevent IHCA and improve survival. The primary objective of this study was to investigate the association between signs of medical distress present within 60 minutes prior to cardiac arrest and survival after cardiac arrest. Methods: The register-based cohort study included adult patients (≥18 years) with IHCA in the Swedish Registry of Cardiopulmonary Resuscitation (SRCR) from 2017-01-01 to 2020–07-15. Signs of distress prior to IHCA were defined as the medical signs arrhythmia, pulmonary oedema, hypotension, hypoxia or seizures present within 60 minutes prior to cardiac arrest (pre-arrest signs). Using multivariable logistic regression, the association between these pre-arrest signs and 30-day survival was analysed in both unadjusted and adjusted models. The covariates used were demographics, comorbidities, characteristics and treatment of cardiac arrest. Results: In total, 8525 patients were included. After adjusting for covariates, patients with arrhythmia had a 58% higher probability of 30-day survival. The adjusted probability of 30-day survival was 41% and 52% lower for patients with hypotension and hypoxia prior to IHCA, respectively. Pulmonary oedema and seizures were not associated with any change in 30-day survival. Conclusions: Among signs of medical distress prior to in-hospital cardiac arrest, arrhythmia was associated with a higher 30-day survival. Hypotension and hypoxia were associated with lower survival after IHCA. These findings indicate that future research on survival after cardiac arrest should take pre-arrest signs into account as it impacts the prerequisites for survival.

Aim: In the event of an out of hospital cardiac arrest (OHCA) it is recommended for a sole untrained bystander to perform compression only CPR (CO-CPR). However, it remains unknown if CO-CPR is inferior to standard CPR (S-CPR), including both compressions and ventilation, in terms of survival. One could speculate that due to the current pandemic, bystanders may be more hesitant performing mouth-to-mouth ventilation. The aim of this study is to assess the association between type of bystander CPR and survival in OHCA. Methods: This study included all patients with a bystander treated OHCA between year 2015–2019 in ages 18–100 using The Swedish Registry for Cardiopulmonary Resuscitation (SRCR). We compared CO-CPR to S-CPR in terms of 30-day survival using a propensity score approach based on machine learning adjusting for a large number of covariates. Results: A total of 13,481 patients were included (5,293 with S-CPR and 8,188 with CO-CPR). The matched subgroup consisted of 2994 cases in each group.Gradient boosting were the best models with regards to predictive accuracy (for type of bystander CPR) and covariate balance. The difference between S-CPR and CO-CPR in all 30 models computed on covariate adjustment and 1-to-1 matching were non-significant. In the 30 weighted models, three comparisons (S-CPR vs. CO-CPR) were significant in terms of improved survival; odds ratio for men was 1.21 (99% confidence interval (CI) 1.02–1.43; Average treatment effect (ATE)); for patients ≥73 years 1.57 (99% CI 1.17–2.12) for Average treatment effect on treated (ATT) and 1.63 (99% CI 1.18–2.25) for ATE. Remaining 27 models showed no differences. No significances remain after adjustment for multiple testing. Conclusion: We found no significant differences between S-CPR and CO-CPR in terms of survival, supporting current recommendations for untrained bystanders regarding CO-CPR.

Objective: Irritable bowel syndrome (IBS) is a chronic pain disorder characterized by disturbed interactions between the gut and the brain with depression as a common comorbidity. In both IBS and depression, structural brain alterations of the insular cortices, key structures for pain processing and interoception, have been demonstrated but the specificity of these findings remains unclear. We compared the gray matter volume (GMV) of insular cortex (IC) subregions in IBS women and healthy controls (HC) and examined relations to gastrointestinal (GI) symptoms and glutamate + glutamine (Glx) concentrations. We further analyzed GMV of IC subregions in women with major depression (MDD) compared to HC and addressed possible differences between depression, IBS, IBS with depression and HC. Design: Women with IBS (n = 75), MDD (n = 41) and their respective HC (n = 39 and n = 43) underwent structural brain MRI. IC subregion volumes were estimated using statistical parametric mapping software. General linear model approaches were applied to IC volumetric data and FDR-corrected partial correlation analyses assessed relations between GMV, GI symptoms and Glx concentrations. Results: IBS patients had significantly smaller IC subregions than HC in both hemispheres but there was no significant difference between MDD compared with IBS and HC for any insular subregion. In IBS, the dorsal anterior insular volumes were negatively correlated with symptoms of nausea and pain, and the left ventral subregion showed a positive correlation with straining to defecate, while the posterior subregion volumes showed no relation to symptoms. In the anterior insula, concentration of Glx showed positive correlations with GMV bilaterally in HC and with GMV of the right anterior insula in IBS. Conclusion: As the interoceptive cortex, the insula shows substantial and disease-specific structural differences in patients with chronic interoceptive visceral pain. Particularly changes in the anterior proportions might be related to chronic exposure to or enhanced salience towards adverse interoceptive visceral signals and could be linked to biochemical changes, calling for further multimodal and longitudinal work.

Natural convection plays a crucial role in latent heat storage system. Determining how natural convection affects the melting of phase change material (PCM) will provide a better understanding of the melting process and give helpful advice on strengthening techniques. The research content of this paper is a mathematical model is established to explain the melting process of PCM affected by natural convection. The mathematical model of phase change melting process is given by introducing the natural convection and the temperature gradient. A coordination factor (Co) based on the mathematical model, which is an instantaneous quantity and proportional to the heat exchange rate and the intensity of natural convection, is introduced to explain the melting process. A square-shaped and shell-tube (concentric, eccentric) PCM heat storage unit were numerically analyzed in more detail. It is found that the Co factor is closely related to the melting rate. It will not promote the melting rate when Co less than 0 while it will promote the melting rate when Co higher than 0, and the higher the Co value, the faster the melting rate. This model gives a clear and quantitative explanation for the problem of melting interface movement affected by natural convection, as well as that increasing the heating temperature and changing only the shape of the heat storage unit can greatly enhance the heat storage rate in this study. The model also provides theoretical guidance for the study of the phase change heat storage enhancement.

In this report, we describe a case of a biphasic tumour which presented as an incidental lump on the wrist of a 78 year old female. The epithelioid component predominated and was strikingly “gland-like”, and in an elderly female raised concerns of a primary soft tissue tumour as well as a metastatic mixed Müllerian tumour. The unusual “gland” lining cells and odd central secretion did not fit classical glands and raised our suspicions of synovial sarcoma. We employed a panel of immunoperoxidase stains to consider synovial sarcoma as well as metastases, and included PAX8, ER and PR for possible gynaecologic and breast malignancies. Paired Box (PAX) 8 is a tissue-specific transcription factor protein, and immunohistochemical stains using antibodies raised against PAX 8 are frequently used in staining panels to help identify the origin of primary or metastatic malignancies, and in particular where tumours from the female genital tract, kidney, thyroid and thymus are included in the differential diagnosis. Our research into PAX8 revealed that it has been little studied in soft tissue sarcomas and there is limited published data in the English language literature regarding PAX8 staining particularly in primary extremity soft tissue synovial sarcomas. Unexpectedly, our panel of immunohistochemical stains showed PAX8 positivity for both the epithelioid and spindle cell components of our case, and again raised concerns of a gynaecological malignancy. The components showed differential PAX8 staining patterns, which is of note, and highlights the possible variability in staining of synovial sarcoma. Definitive diagnosis of biphasic synovial sarcoma was confirmed by fluorescent in situ hybridisation studies. This case report therefore documents PAX8 positive staining in biphasic primary soft tissue synovial sarcoma, demonstrating important considerations in its use, enabling the diagnosis of this infrequent and potentially aggressive soft tissue tumour. The relevant literature is highlighted. The variable range of appearances of this potentially aggressive tumour is further illustrated by our case which showed striking epithelial-rich morphology, and presented important diagnostic considerations. Careful morphologic examination together with immunohistochemical and molecular studies in our case enabled a definitive diagnosis of this histologically striking variant, with unexpected PAX8 positive staining.

This review emphasizes that much geological data has a context, and properties of quality (reliability, precision) that are sometimes overlooked. A review of a pair of wells is e-appraised to examine the lithostratigraphic formations and seismostratigraphic “Groups” commonly used to describe Malay Basin Cenozoic stratigraphy. A new interpretation of the wells helps to develop an objective, genetic stratigraphic framework. Such an evidence-based framework is superior to both the old formation concepts, and the seismostratigraphic horizons, neither of which are part of a predictive facies model that allowed testing, or integration with other stratigraphic disciplines. The tectono-stratigraphic framework that is described here correlates very well with regional tectonic models. It also appears to have no link to eustatic sea-level changes until the mid-Pliocene, after which a strong glacio-eustatic signal is observed.The new inductive model asks fundamental questions about the deposition and palaeographic distribution of an important oil reservoir (the J Sand, Lower Ledang Sand, or Pasir Sandstone). It also questions how we should interpret seismic, and how we should replace idealised (deductive) models with evidence-based methods. As exploration in a mature area relies on subtle plays with stratigraphic components it is essential to have a tested and scientifically defendable stratigraphic framework.

Automated in-process Non-Destructive Testing (NDT) systems are rapidly gaining traction within the manufacturing industry as they reduce manufacturing time and costs. When considering calibration and verification of such systems, creating defects of known geometry and nature during the deposition of a weld can: (I) help examine the capability of the automated system to detect and characterise defects, (II) be used to form a database of signals associated with different defect types to train intelligent defect classification algorithms, and (III) act as a basis for in-process gain calibration during weld inspection at high temperatures, where the ultrasound beam can be skewed as a result of velocity gradients. In view of this, this paper investigates two unique methodologies for introducing: (a) lack of fusion weld defects by embedding tungsten in the weld and (b) creating artificial weld cracks by quenching to imitate the real cracking scenarios. According to the results of Phased Array Ultrasound Testing (PAUT) inspections, the methodologies used for embedding the artificial defects were successful. The validity of inspections was also verified by extracting micrographs from the defective sections of the welds, and model-based simulations were carried out to gain a better understanding of the wave propagation path and interaction with the generated defects.

Strong acid accidental ingestion is a common case in rural society and children. The effect of strong acids may cause injuries of the gastrointestinal tract. We present a case obstruction in the distal part of gastric after accidental sulfuric acid ingestion in children. Sulfuric acid ingestion is potential in children since its commercial product physical appearance looks like drink water. Then the patient was diagnosed with pyloric obstruction after barium meal examination and was treated using Jaboulay gastroduodenostomy procedure.

This paper assesses how interventions utilising material apparatus can drive food waste reduction in professional kitchens. Using non-participant observation and interviews, this study evaluated work-based experiments to cut waste in luxury hotels. The paper focuses on the impacts of one specific intervention: the introduction of small, transparent food waste bins, positioned at each food preparation station. The findings examine how the material properties of these apparatus, including size, calibration and transparency, coupled with their location, shaped chefs' food waste related practices. Moreover, the findings show how chefs' organisational and occupational norms interact with the influence exerted by utensils to create new meanings and assign value to food, waste and the craft skills used to reduce it.

Background: Current recommendations for valve size selection are based on multidimensional annular measurements, yet the overlap between two different transcatheter heart valve (THV) sizes remains. We sought to evaluate whether undersizing but overfilling eliminates the gray zones of valve sizing. Methods: Data of 246 consecutive patients undergoing transcatheter aortic valve replacement (TAVR) with the balloon-expandable bioprosthesis with either conventional sizing and nominal filling (group 1 (NF-TAVR), n = 154) or undersizing but overfilling under a Less Is More (LIM)-Principle (group 2 (LIM-TAVR), n = 92) were compared. Paravalvular leakage (PVL) was graded angiographically and quantitatively using invasive hemodynamics. Results: Annulus rupture (AR) occurred only in group 1 (n = 3). Due to AR adequate evaluation of PVL was possible in 152 patients of group 1. More than mild PVL was found in 13 (8.6%) patients of group 1 and 1 (1.1%) patient of group 2 (p = 0.019). Postdilatation was performed in 31 (20.1%) patients of group 1 and 6 patients (6.5%) of group 2 (p = 0.003). For patients with borderline annulus size in group 1 (n = 35, 22.7%) valve size selection was left to the physiciańs choice resulting in selection of the larger prosthesis in 10 (28.6%). In group 2 all patients with borderline annulus (n = 36, 39.1%) received the smaller prosthesis (LIM-TAVR). The postprocedural mean transvalvular pressure gradient was significantly higher in the NF-TAVR-group (11.7 ± 4 vs. 10.1 ± 3.6 mmHg, p = 0.005). Conclusion: LIM-TAVR eliminates the gray zones of sizing and associated PVL, can improve THV-performance, reduce incidence of annular rupture and simplify the procedure especially in borderline cases.

The YOUth cohort study is a unique longitudinal study on brain development in the general population. As part of the YOUth study, 2000 children will be included at 8, 9 or 10 years of age and planned to return every three years during adolescence. Magnetic resonance imaging (MRI) brain scans are collected, including structural T1-weighted imaging, diffusion-weighted imaging (DWI), resting-state functional MRI and task-based functional MRI. Here, we provide a comprehensive report of the MR acquisition in YOUth Child & Adolescent including the test-retest reliability of brain measures derived from each type of scan. To measure test-retest reliability, 17 adults were scanned twice with a week between sessions using the full YOUth MRI protocol. Intraclass correlation coefficients were calculated to quantify reliability. Global brain measures derived from structural T1-weighted and DWI scans were reliable. Resting-state functional connectivity was moderately reliable, as well as functional brain measures for both the inhibition task (stop versus go) and the emotion task (face versus house). Our results complement previous studies by presenting reliability results of regional brain measures collected with different MRI modalities. YOUth facilitates data sharing and aims for reliable and high-quality data. Here we show that using the state-of-the art YOUth MRI protocol brain measures can be estimated reliably.

Summary: Objectives: To investigate the association between having osteoarthritis (OA), hypertension, or diabetes, either alone or in combination, and receiving guideline-recommended exercise or weight-reduction advice. Design: Cross-sectional study. Methods: We applied logistic regression to analyse self-reported data from the 2017 Danish National Health survey (DNHS). We calculated the proportions and odds ratios of receiving exercise advice and weight-reduction advice (if BMI>30) from the general practitioner (GP) in seven patient groups: those with OA or hypertension or diabetes or any combination of these diseases. Results: From the 183,372 DNHS responders, we included 71,717 patients (≥45 years) who reported consulting a GP during the previous year. Among patients with only one disease, those with OA were least likely to receive exercise advice (13%, 1441/11,024) and weight-reduction advice (27%, 504/1877), while those with diabetes were most likely to receive these advice (32%, 387/1200 and 55%, 160/289, respectively).For OA-only patients, the adjusted odds ratios of receiving exercise advice and weight-reduction advice were 1.4 (95% CI 1.3 to 1.5) and 1.6 (95% CI 1.4 to 1.8), respectively, compared with patients with none of the three diseases. For diabetes-only patients, the adjusted odds ratios were 4.2 (95% CI 3.7 to 4.7) and 5.4 (95% CI 4.2 to 7.0), respectively. Conclusion: Few patients with OA self-reported having received guideline-recommended exercise advice, or weight-reduction advice if obese, from their GP. Furthermore, patients with OA were less likely to report having received these advice compared with patients with other chronic diseases.

Cardiac amyloidosis (CA) has emerged as a previously underestimated cause of heart failure and mortality. Underdiagnosis resulted mainly from unawareness of the true disease prevalence and the non-specific symptoms of the disease. CA results from extracellular deposition of misfolded protein fibrils, commonly derived from transthyretin (ATTR) or immunoglobulin light chains (AL). A significant proportion of older patients with heart failure and other extracardiac manifestations suffer from ATTR-CA, whereas AL-CA is still considered a rare disease. This article provides an overview of CA with a special focus on current and emerging diagnostic modalities. Furthermore, we provide a diagnostic algorithm for the evaluation of patients with suspected CA in every-day practice.

Additive manufacturing (AM) has the capability to build complex parts with internal features, which have many advantages over conventionally manufactured parts. This makes AM an alternative for advanced manufacturing sectors. AM components suffer from defects due to the lack of understanding in the build process. This makes the adaptation of AM in safety-critical industries, such as aerospace, problematic. The current AM work flow calls for costly off-line inspections to qualify components as defect-free. The layer by layer nature of the AM provides an opportunity for an on-line inspection to take place. This can provide early detection of defects as well as information for optimization and repair of the build. Laser Induced Phased Arrays (LIPA) present themselves as a viable remote, non-destructive, ultrasonic technique capable of being implemented as part of an on-line inspection of AM. Lasers are used to generate and detect ultrasound and a phased array is synthesized in post-processing. This paper demonstrates the capability of LIPA to successfully detect and locate features within AM components off-line. Cylindrical features as small as 0.2 mm in diameter and 26 mm above the inspection surface were detected using LIPA and verified using X-ray computed tomography (XCT). Keywords: Additive manufacturing, Laser Induced Phased Array, Non-destructive, Non-contact, Selective laser melting, Geometrical accuracy

Depression in young adults is a growing concern to public health. This study aims to investigate if depression status in young adults is related to clinical and behavioral cardiovascular disease (CVD) risk factors. Cross-sectional data from a population-based sample of young Danish adults participating in the European Youth Heart Study 2009–2010 were used to examine this (n = 644, mean age 24.3 years 47% male). Measures of cardiorespiratory fitness (CRF), body composition, blood pressure, fasting levels of high and low density lipids (HDL, LDL), insulin, and glucose were obtained. Symptoms of depression were obtained using the Major Depression Inventory scale. Information on sleep disorders; drinking and smoking habits were obtained by questionnaires. Associations of depression with CVD risk factors were examined using logistic and linear regression adjusted for age and sex. Prevalence of mild-moderate-severe depression was 8.7% (5.6% males, 11.5% females). Significant sex differences were found in the association between several CVD risk factors and depression status. Women with depression had higher odds of overweight (OR = 2.2, 95%CI: 1.01–4.0), abdominal adiposity (OR = 2.5, 95%CI: 1.2–4.8), low CRF (OR = 2.5, 95%CI: 1.2–5.5), insulin resistance (OR = 2.3, 95%CI: 1.1–4.6), low HDL (OR = 2.0, 95%CI: 1.01–4.1) and high LDL (OR = 2.2, 95%CI: 1.04–4.5) compared to women without depression. Men with depression had significantly increased odds of having high blood pressure and being smokers compared to men without depression (OR: 3.1, 95%CI: 1.1–8.8 and OR: 3.0, 95%CI: 1.1–8.4, respectively). Depression symptoms in young adulthood were related to unfavorable clinical- and behavioral CVD risk factors, particularly in women. Keywords: Depression, Cardiovascular disease risk, Behavioral risk, Young adults, EYHS, Gender

Objectives: To qualitatively evaluate late dynamic contrast phases, 10, 20 and 30 min, after administration of Gd-EOB-DTPA with regard to biliary excretion in patients presenting with elevated liver enzymes without clinical signs of cirrhosis or hepatic decompensation and to compare the visual assessment of contrast agent excretion with histo-pathological fibrosis stage, contrast uptake parameters and blood tests. Methods: 29 patients were prospectively examined using 1.5 T MRI. The visually assessed presence or absence of contrast agent for each of five anatomical regions in randomly reviewed time-series was summarized on a four grade scale for each patient. The scores, including a total visual score, were related to the histo-pathological findings, the quantitative contrast agent uptake parameters, expressed as KHep or LSC_N, and blood tests. Results: No relationship between the fibrosis grade or contrast uptake parameters could be established. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found. Comparing a sub-group of cholestatic patients with fibrosis score and Gd-EOB-DTPA dynamic parameters did not add any additional significant correlation. Conclusions: No correlation between visually assessed biliary excretion of Gd-EOB-DTPA and histo-pathological or contrast uptake parameters was found. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found.

Purpose: Continuous monitoring of liver fibrosis progression in patients is not feasible with the current diagnostic golden standard (needle biopsy). Recently, magnetic resonance elastography (MRE) has emerged as a promising method for such continuous monitoring. Since there are different MRE methods that could be used in a clinical setting there is a need to investigate whether measurements produced by these MRE methods are comparable. Hence, the purpose of this pilot study was to evaluate whether the measurements of the viscoelastic properties produced by 2D (stiffness) and 3D (elasticity and ‘Gabs,Elastic’) MRE are comparable. Materials and methods: Seven patients with diffuse or suspect diffuse liver disease were examined in the same day with the two MRE methods. 2D MRE was performed using an acoustic passive transducer, with a 1.5 T GE 450 W MR system. 3D MRE was performed using an electromagnetic active transducer, with a 1.5 T Philips Achieva MR system. Finally, mean viscoelastic values were extracted from the same anatomical region for both methods by an experienced radiologist. Results: Stiffness correlated well with the elasticity, R2 = 0.96 (P

Objective: We aimed at validating a plasma biomarker for neuronal damage that can be used in acute and chronic models of neurological diseases. Methods: We investigated two different models, middle cerebral artery occlusion followed by reperfusion and MOG35–55-induced experimental autoimmune encephalomyelitis (EAE). In stroke experiments we measured infarct sizes by magnetic resonance imaging and vital stainings and correlated them with plasma levels of neuron specific enolase (NSE) at different time points after reperfusion. Equally, in EAE experiments, we correlated NSE levels with neurological scores and histopathological damage of axons at different time points. We detected plasma NSE levels by ELISA. Results: Plasma NSE levels correlated significantly with stroke size, EAE score and histopathological damage in EAE. Investigations into the dynamics of neuronal loss over time correlated well with the dynamics of NSE levels. NSE even predicted the onset of EAE, before clinical signs were recordable. Conclusions: Plasma NSE is a valid and simple experimental biomarker that allows quantifying the degree of neuronal injury in a non-invasive approach.